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Entry version 164 (13 Feb 2019)
Sequence version 2 (01 May 2000)
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Protein

Laforin

Gene

EPM2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Plays an important role in preventing glycogen hyperphosphorylation and the formation of insoluble aggregates, via its activity as glycogen phosphatase, and by promoting the ubiquitination of proteins involved in glycogen metabolism via its interaction with the E3 ubiquitin ligase NHLRC1/malin. Shows strong phosphatase activity towards complex carbohydrates in vitro, avoiding glycogen hyperphosphorylation which is associated with reduced branching and formation of insoluble aggregates (PubMed:16901901, PubMed:23922729, PubMed:26231210, PubMed:25538239, PubMed:25544560). Dephosphorylates phosphotyrosine and synthetic substrates, such as para-nitrophenylphosphate (pNPP), and has low activity with phosphoserine and phosphothreonine substrates (in vitro) (PubMed:11001928, PubMed:11220751, PubMed:11739371, PubMed:14532330, PubMed:16971387, PubMed:18617530, PubMed:22036712, PubMed:23922729, PubMed:14722920). Has been shown to dephosphorylate MAPT (By similarity). Forms a complex with NHLRC1/malin and HSP70, which suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system (UPS). Acts as a scaffold protein to facilitate PPP1R3C/PTG ubiquitination by NHLRC1/malin (PubMed:23922729). Also promotes proteasome-independent protein degradation through the macroautophagy pathway (PubMed:20453062).By similarity17 Publications
Isoform 2: does not bind to glycogen (PubMed:18617530). Lacks phosphatase activity and might function as a dominant-negative regulator for the phosphatase activity of isoform 1 and isoform 7 (PubMed:18617530, PubMed:22036712).2 Publications
Isoform 7: has phosphatase activity (in vitro).1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei32SubstrateCombined sources1 Publication1
Binding sitei87SubstrateCombined sources1 Publication1
Binding sitei197SubstrateCombined sources1 Publication1
Binding sitei235SubstrateCombined sources1 Publication1
Binding sitei241SubstrateCombined sources1 Publication1
<p>This subsection of the ‘Function’ section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei266Phosphocysteine intermediatePROSITE-ProRule annotation6 Publications1
Binding sitei304SubstrateCombined sources1 Publication1
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections (‘Function’, ‘PTM / Processing’, ‘Pathology and Biotech’) according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei329Required for homodimerization1 Publication1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionHydrolase, Protein phosphatase
Biological processAutophagy, Carbohydrate metabolism, Glycogen metabolism

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
3.1.3.16 2681

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-3322077 Glycogen synthesis
R-HSA-3785653 Myoclonic epilepsy of Lafora

SIGNOR Signaling Network Open Resource

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SIGNORi
O95278

Protein family/group databases

Carbohydrate-Active enZymes

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CAZyi
CBM20 Carbohydrate-Binding Module Family 20

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Laforin1 Publication (EC:3.1.3.-5 Publications, EC:3.1.3.161 Publication, EC:3.1.3.482 Publications)
Alternative name(s):
Glucan phosphatase2 Publications
Glycogen phosphatase2 Publications
Lafora PTPase
Short name:
LAFPTPase1 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:EPM2A
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 6

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000112425.13

Human Gene Nomenclature Database

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HGNCi
HGNC:3413 EPM2A

Online Mendelian Inheritance in Man (OMIM)

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MIMi
607566 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_O95278

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Epilepsy, progressive myoclonic 2 (EPM2)14 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive and severe form of adolescent-onset progressive epilepsy. Typically, as seizures increase in frequency, cognitive function declines towards dementia, and affected individuals die usually within 10 years after onset. EPM2 occurs worldwide, but it is particularly common in the mediterranean countries of southern Europe and northern Africa, in southern India and in the Middle East. At the cellular level, it is characterized by accumulation of starch-like polyglucosans called Lafora bodies (LBs) that are most abundant in organs with the highest glucose metabolism: brain, heart, liver and skeletal muscle. Among other conditions involving polyglucosans, EPM2 is unique in that the inclusions are in neuronal dendrites but not axons and the forming polyglucosan fibrils are associated with the endoplasmic reticulum.
See also OMIM:254780
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_01946525S → P in EPM2; atypical form; does not affect glycogen binding. 2 Publications1
Natural variantiVAR_01946628E → K in EPM2; does not affect glycogen binding. 1 Publication1
Natural variantiVAR_01946732W → G in EPM2; impairs protein stability; affects phosphatase activity; abolishes glycogen binding; abolishes phosphatase activity with insoluble glucan; disrupts the interaction with PPP1R3C. 6 PublicationsCorresponds to variant dbSNP:rs104893955EnsemblClinVar.1
Natural variantiVAR_01946984F → L in EPM2; affects phosphatase activity and glycogen binding; disrupts the interaction with PPP1R3C. 2 PublicationsCorresponds to variant dbSNP:rs1362231306Ensembl.1
Natural variantiVAR_01947088F → L in EPM2; does not affect glycogen binding. 1 PublicationCorresponds to variants dbSNP:rs1034706422 and dbSNP:rs1463000703EnsemblEnsembl.1
Natural variantiVAR_01947191R → P in EPM2; atypical form; learning difficuties with childhood-onset. 2 Publications1
Natural variantiVAR_019472108R → C in EPM2; loss of phosphatase activity; reduced self-interaction capacity; disrupts the interaction with PPP1R3C. 3 PublicationsCorresponds to variant dbSNP:rs137852915EnsemblClinVar.1
Natural variantiVAR_046383140K → N in EPM2. 1 Publication1
Natural variantiVAR_046384148N → Y in EPM2. 1 Publication1
Natural variantiVAR_019474171R → H in EPM2; results in ubiquitin-positive perinuclear aggregates; no effect on glycogen binding; abolishes phosphatase activity; may affect proper folding. 5 PublicationsCorresponds to variant dbSNP:rs137852916EnsemblClinVar.1
Natural variantiVAR_019475187T → A in EPM2; abolishes interaction with NHLRC1. 1 Publication1
Natural variantiVAR_019476194T → I in EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; reduced self-interaction capacity; abolishes interaction with NHLRC1, PPP1R3C and PRKAA2; no effect on phosphorylation of protein. 3 PublicationsCorresponds to variant dbSNP:rs375544596Ensembl.1
Natural variantiVAR_046385210E → K in EPM2. 1 Publication1
Natural variantiVAR_019477240G → S in EPM2; impaired phosphatase activity; does not affect glycogen binding; disrupts the interaction with PPP1R3C. 3 Publications1
Natural variantiVAR_019478279G → S in EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 5 PublicationsCorresponds to variant dbSNP:rs137852917EnsemblClinVar.1
Natural variantiVAR_019479293Q → L in EPM2; results in ubiquitin-positive perinuclear aggregates; may affect proper folding; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 4 PublicationsCorresponds to variant dbSNP:rs796052427EnsemblClinVar.1
Natural variantiVAR_019480294Y → N in EPM2; results in ubiquitin-positive perinuclear aggregates; impairs phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 4 Publications1
Natural variantiVAR_019481301P → L in EPM2; impairs protein stability; impairs phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 3 PublicationsCorresponds to variant dbSNP:rs796052428Ensembl.1
Natural variantiVAR_046386310L → W in EPM2; causes location of isoform 1 at cytoplasmic punctae; does not affect homodimerization of isoform 1 but prevents heterodimerization of isoform 1 and isoform 2. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi8V → A: Loss of phosphatase activity. No effect on glycogen binding. 1 Publication1
Mutagenesisi25S → A: Partial loss of phosphatase activity. Abolishes homodimerization. Abolishes interaction with NHLRC1, PPP1R3C and PRKAA2. Does not affect glycogen binding. Reduces stability of the protein. 1 Publication1
Mutagenesisi25S → D: Partial loss of phosphatase activity. Increases interaction with NHLRC1. Does not affect interaction with NHLRC1, PPP1R3C or PRKAA2. Does not affect binding to carbohydrate. Does not affect homodimerization. 1 Publication1
Mutagenesisi87K → A: Loss of phosphatase activity. Abolishes glycogen binding. 2 Publications1
Mutagenesisi99W → A: Strongly reduces phosphatase activity. Strongly reduces glycogen binding. 1 Publication1
Mutagenesisi109 – 110CC → SS: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication2
Mutagenesisi123C → S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication1
Mutagenesisi126I → T: Strongly decreased phosphatase activity. No effect on glycogen binding. 1 Publication1
Mutagenesisi142T → A: Strongly decreased phosphatase activity. No effect on glycogen binding. 1 Publication1
Mutagenesisi168S → A or D: Abolishes interaction with NHLRC1. 1 Publication1
Mutagenesisi169C → S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication1
Mutagenesisi169C → S: No effect on phosphatase activity. 1 Publication1
Mutagenesisi171R → A: No effect on phosphatase activity. 1 Publication1
Mutagenesisi187T → D: Abolishes interaction with NHLRC1. 1 Publication1
Mutagenesisi194T → D: Does not affect interaction with NHLRC1, PPP1R3C or PRKAA2. 1 Publication1
Mutagenesisi197D → A: Strongly decreased phosphatase activity. No effect on glycogen binding. 2 Publications1
Mutagenesisi205C → S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication1
Mutagenesisi235D → A: Complete loss of phosphatase activity. Does not affect glycogen binding. 2 Publications1
Mutagenesisi236M → A: Complete loss of phosphatase activity. No effect on glycogen binding. 1 Publication1
Mutagenesisi250C → S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication1
Mutagenesisi251L → A: Impairs protein stability. Strongly reduces phosphatase activity. No effect on glycogen binding. 1 Publication1
Mutagenesisi266C → S: Complete loss of phosphatase activity. Does not affect glycogen binding. Does not affect self-interaction. Increases the interaction with PPP1R3C. 7 Publications1
Mutagenesisi272R → A: Complete loss of phosphatase activity. 1 Publication1
Mutagenesisi321F → S: Impairs protein stability. Strongly reduces phosphatase activity. No effect on glycogen binding. 1 Publication1
Mutagenesisi329 – 331Missing : Fails to homodimerize. Does not affect carbohydrate binding or phosphatase activity. 1 Publication3
Mutagenesisi329C → S: Fails to homodimerize. Does not affect carbohydrate binding, interaction with NHLRC1, phosphatase activity, or ubiquitination by NHLRC1. 1 Publication1
Mutagenesisi329C → S: No effect on homodimerization. 1 Publication1

Keywords - Diseasei

Disease mutation, Epilepsy, Glycogen storage disease

Organism-specific databases

DisGeNET

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DisGeNETi
7957

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

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GeneReviewsi
EPM2A

MalaCards human disease database

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MalaCardsi
EPM2A
MIMi254780 phenotype

Open Targets

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OpenTargetsi
ENSG00000112425

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
501 Lafora disease

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA27832

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL2311242

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
EPM2A

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000948381 – 331LaforinAdd BLAST331

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei25Phosphoserine; by AMPK1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Polyubiquitinated by NHLRC1/malin.1 Publication
Phosphorylation on Ser-25 by AMPK affects the phosphatase activity of the enzyme and its ability to homodimerize and interact with NHLRC1, PPP1R3C or PRKAA2.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
O95278

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
O95278

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
O95278

PeptideAtlas

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PeptideAtlasi
O95278

PRoteomics IDEntifications database

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PRIDEi
O95278

ProteomicsDB human proteome resource

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ProteomicsDBi
50779
50780 [O95278-2]
50782 [O95278-4]
50783 [O95278-5]
50784 [O95278-6]
50785 [O95278-7]
50786 [O95278-8]

PTM databases

DEPOD human dephosphorylation database

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DEPODi
O95278

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
O95278

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
O95278

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed in heart, skeletal muscle, kidney, pancreas and brain. Isoform 4 is also expressed in the placenta.2 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000112425 Expressed in 222 organ(s), highest expression level in skeletal muscle tissue of rectus abdominis

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
O95278 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
O95278 HS

Organism-specific databases

Human Protein Atlas

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HPAi
HPA053643
HPA055468

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer (PubMed:16971387, PubMed:18617530, PubMed:23922729, PubMed:25538239, PubMed:25544560). Interacts with itself (PubMed:14532330). Interacts with PPP1R3B, PPP1R3C, PPP1R3D, HIRIP5, and EPM2AIP1 (PubMed:12782127, PubMed:12915448, PubMed:14532330, PubMed:16901901, PubMed:18070875). Binds glycogen and Lafora bodies (PubMed:11739371, PubMed:14532330, PubMed:14706656, PubMed:15102711, PubMed:18617530, PubMed:22036712). Interacts with NHLRC1/malin (via the NHL repeats) (PubMed:15930137, PubMed:22036712, PubMed:23922729). Forms a complex with NHLRC1/malin and HSP70 (PubMed:19036738). Interacts with PPP1R3D; in the presence of NHLC1/malin the interaction leads to ubiquitination and autophagic degradation of PPP1R3D. Interacts (via the phosphatase domain) with MAPT/Tau; the interaction dephosphorylates MAPT (PubMed:19542233). Isoform 1 and isoform 2 interact to form a heterodimeric complex that lacks phosphatase activity (in vitro) (PubMed:18617530). Active phosphatase isoform 7 and isoform 1 interact with each other, but give rise to lower phosphatase activity than isoform 1 or isoform 7 by themselves (in vitro) (PubMed:22036712). Active phosphatase isoform 7 and inactive isoform 2 interact with each other, but give rise to lower phosphatase activity than isoform 7 by itself (in vitro) (PubMed:22036712). Interacts with PRDM8 (PubMed:22961547).18 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
113679, 23 interactors

Protein interaction database and analysis system

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IntActi
O95278, 4 interactors

STRING: functional protein association networks

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STRINGi
9606.ENSP00000356489

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
O95278

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1331
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4R30X-ray2.30A/B/C/D148-331[»]
4RKKX-ray2.40A/C1-329[»]

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
O95278

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
O95278

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini1 – 124CBM20PROSITE-ProRule annotationAdd BLAST124
Domaini243 – 311Tyrosine-protein phosphataseAdd BLAST69

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni103 – 107Substrate bindingCombined sources1 Publication5
Regioni267 – 272Substrate bindingCombined sources1 Publication6

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi266 – 272Glucan phosphatase signature motif CXAGXGR2 Publications7

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The CBM20 domain mediates binding to cytoplasmic glycogen and to Lafora polyglucosan bodies.2 Publications

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG1716 Eukaryota
COG2453 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00390000010101

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000285975

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG051493

KEGG Orthology (KO)

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KOi
K14165

Identification of Orthologs from Complete Genome Data

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OMAi
RKVQYFV

Database of Orthologous Groups

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OrthoDBi
692580at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
O95278

TreeFam database of animal gene trees

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TreeFami
TF332841

Family and domain databases

Conserved Domains Database

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CDDi
cd05806 CBM20_laforin, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
2.60.40.10, 1 hit
3.90.190.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR013784 Carb-bd-like_fold
IPR034831 CBM20_laforin
IPR002044 CBM_fam20
IPR000340 Dual-sp_phosphatase_cat-dom
IPR024950 DUSP
IPR013783 Ig-like_fold
IPR029021 Prot-tyrosine_phosphatase-like
IPR016130 Tyr_Pase_AS
IPR000387 TYR_PHOSPHATASE_dom
IPR020422 TYR_PHOSPHATASE_DUAL_dom

The PANTHER Classification System

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PANTHERi
PTHR10159 PTHR10159, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF00686 CBM_20, 1 hit
PF00782 DSPc, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM01065 CBM_2, 1 hit
SM00195 DSPc, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF49452 SSF49452, 1 hit
SSF52799 SSF52799, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS51166 CBM20, 1 hit
PS00383 TYR_PHOSPHATASE_1, 1 hit
PS50056 TYR_PHOSPHATASE_2, 1 hit
PS50054 TYR_PHOSPHATASE_DUAL, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (8+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 8 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

This entry has 8 described isoforms and 9 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O95278-1) [UniParc]FASTAAdd to basket
Also known as: A, LDH11 Publication, Laf3311 Publication

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MRFRFGVVVP PAVAGARPEL LVVGSRPELG RWEPRGAVRL RPAGTAAGDG
60 70 80 90 100
ALALQEPGLW LGEVELAAEE AAQDGAEPGR VDTFWYKFLK REPGGELSWE
110 120 130 140 150
GNGPHHDRCC TYNENNLVDG VYCLPIGHWI EATGHTNEMK HTTDFYFNIA
160 170 180 190 200
GHQAMHYSRI LPNIWLGSCP RQVEHVTIKL KHELGITAVM NFQTEWDIVQ
210 220 230 240 250
NSSGCNRYPE PMTPDTMIKL YREEGLAYIW MPTPDMSTEG RVQMLPQAVC
260 270 280 290 300
LLHALLEKGH IVYVHCNAGV GRSTAAVCGW LQYVMGWNLR KVQYFLMAKR
310 320 330
PAVYIDEEAL ARAQEDFFQK FGKVRSSVCS L
Length:331
Mass (Da):37,158
Last modified:May 1, 2000 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iDD79F917262AB458
GO
Isoform 2 (identifier: O95278-2) [UniParc]FASTAAdd to basket
Also known as: B, C-terISO, Laf3171 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     310-320: LARAQEDFFQK → ASQDTFPL
     321-331: Missing.

Note: Produced by alternative splicing.
Show »
Length:317
Mass (Da):35,519
Checksum:i5646A039398AC24D
GO
Isoform 4 (identifier: O95278-4) [UniParc]FASTAAdd to basket
Also known as: Laf1521 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     102-199: NGPHHDRCCT...MNFQTEWDIV → IASRRLPPAQ...VPAHSPGDLG
     200-331: Missing.

Note: Produced by alternative splicing. May be due to an intron retention.
Show »
Length:152
Mass (Da):15,804
Checksum:i60CD9293F2267EC4
GO
Isoform 5 (identifier: O95278-5) [UniParc]FASTAAdd to basket
Also known as: Laf2241 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     160-293: Missing.
     294-331: YFLMAKRPAV...GKVRSSVCSL → PSTDAAPGGV...PHGQEAGCLH

Note: Produced by alternative splicing.
Show »
Length:224
Mass (Da):24,134
Checksum:i66ECE43870086B2A
GO
Isoform 6 (identifier: O95278-6) [UniParc]FASTAAdd to basket
Also known as: Laf881 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-243: Missing.

Note: Produced by alternative initiation at Met-244 of isoform 1. Transcript amplified but protein not detected.1 Publication
Show »
Length:88
Mass (Da):9,933
Checksum:iD28FAB18CC285D07
GO
Isoform 7 (identifier: O95278-7) [UniParc]FASTAAdd to basket
Also known as: Laf1771 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-159: MRFRFGVVVP...AGHQAMHYSR → MIFNK

Note: Produced by alternative splicing. Active phosphatase.1 Publication
Show »
Length:177
Mass (Da):20,256
Checksum:i5AE29B26B72E7BF7
GO
Isoform 8 (identifier: O95278-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-138: Missing.

Note: Produced by alternative splicing. No experimental confirmation available.
Show »
Length:193
Mass (Da):22,160
Checksum:i3DC9436A9885B915
GO
Isoform 9 (identifier: B3EWF7-1) [UniParc]FASTAAdd to basket
Also known as: POCR1 Publication
The sequence of this isoform can be found in the external entry B3EWF7.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Produced by alternative initiation. Arises due to the use of an alternative initiation codon in exon 1 out of frame with isoform 1 and results in a completely different isoform.
Length:344
Mass (Da):35,169
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B3EWF7EP2A2_HUMAN
Laforin, isoform 9
EPM2A
344Annotation score:

Annotation score:4 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0Y6I8H0Y6I8_HUMAN
Laforin, isoform 9
EPM2A
317Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0Y7S8H0Y7S8_HUMAN
Laforin, isoform 9
EPM2A
144Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A1W2PQ84A0A1W2PQ84_HUMAN
Laforin, isoform 9
EPM2A
127Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A1W2PPT8A0A1W2PPT8_HUMAN
Laforin, isoform 9
EPM2A
209Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A1W2PRS5A0A1W2PRS5_HUMAN
Laforin, isoform 9
EPM2A
134Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A1W2PPJ6A0A1W2PPJ6_HUMAN
Laforin, isoform 9
EPM2A
86Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A1W2PP62A0A1W2PP62_HUMAN
Laforin, isoform 9
EPM2A
18Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A1W2PRC9A0A1W2PRC9_HUMAN
Laforin, isoform 9
EPM2A
70Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AAO15523 differs from that shown. Probable cloning artifact.Curated
The sequence BAG51107 differs from that shown. Reason: Frameshift at position 223.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti193Q → K in AAH70047 (PubMed:15489334).Curated1
Sequence conflicti248A → P in AAO15523 (Ref. 4) Curated1
Sequence conflicti258K → E in BAG61454 (PubMed:14702039).Curated1
Sequence conflicti294Y → H in BAG61454 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01946525S → P in EPM2; atypical form; does not affect glycogen binding. 2 Publications1
Natural variantiVAR_01946628E → K in EPM2; does not affect glycogen binding. 1 Publication1
Natural variantiVAR_01946732W → G in EPM2; impairs protein stability; affects phosphatase activity; abolishes glycogen binding; abolishes phosphatase activity with insoluble glucan; disrupts the interaction with PPP1R3C. 6 PublicationsCorresponds to variant dbSNP:rs104893955EnsemblClinVar.1
Natural variantiVAR_01946846A → P Does not affect glycogen binding. 3 PublicationsCorresponds to variant dbSNP:rs374338349EnsemblClinVar.1
Natural variantiVAR_01946984F → L in EPM2; affects phosphatase activity and glycogen binding; disrupts the interaction with PPP1R3C. 2 PublicationsCorresponds to variant dbSNP:rs1362231306Ensembl.1
Natural variantiVAR_01947088F → L in EPM2; does not affect glycogen binding. 1 PublicationCorresponds to variants dbSNP:rs1034706422 and dbSNP:rs1463000703EnsemblEnsembl.1
Natural variantiVAR_01947191R → P in EPM2; atypical form; learning difficuties with childhood-onset. 2 Publications1
Natural variantiVAR_019472108R → C in EPM2; loss of phosphatase activity; reduced self-interaction capacity; disrupts the interaction with PPP1R3C. 3 PublicationsCorresponds to variant dbSNP:rs137852915EnsemblClinVar.1
Natural variantiVAR_019473114E → D1 Publication1
Natural variantiVAR_046383140K → N in EPM2. 1 Publication1
Natural variantiVAR_046384148N → Y in EPM2. 1 Publication1
Natural variantiVAR_019474171R → H in EPM2; results in ubiquitin-positive perinuclear aggregates; no effect on glycogen binding; abolishes phosphatase activity; may affect proper folding. 5 PublicationsCorresponds to variant dbSNP:rs137852916EnsemblClinVar.1
Natural variantiVAR_019475187T → A in EPM2; abolishes interaction with NHLRC1. 1 Publication1
Natural variantiVAR_019476194T → I in EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; reduced self-interaction capacity; abolishes interaction with NHLRC1, PPP1R3C and PRKAA2; no effect on phosphorylation of protein. 3 PublicationsCorresponds to variant dbSNP:rs375544596Ensembl.1
Natural variantiVAR_046385210E → K in EPM2. 1 Publication1
Natural variantiVAR_019477240G → S in EPM2; impaired phosphatase activity; does not affect glycogen binding; disrupts the interaction with PPP1R3C. 3 Publications1
Natural variantiVAR_019478279G → S in EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 5 PublicationsCorresponds to variant dbSNP:rs137852917EnsemblClinVar.1
Natural variantiVAR_019479293Q → L in EPM2; results in ubiquitin-positive perinuclear aggregates; may affect proper folding; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 4 PublicationsCorresponds to variant dbSNP:rs796052427EnsemblClinVar.1
Natural variantiVAR_019480294Y → N in EPM2; results in ubiquitin-positive perinuclear aggregates; impairs phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 4 Publications1
Natural variantiVAR_019481301P → L in EPM2; impairs protein stability; impairs phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 3 PublicationsCorresponds to variant dbSNP:rs796052428Ensembl.1
Natural variantiVAR_046386310L → W in EPM2; causes location of isoform 1 at cytoplasmic punctae; does not affect homodimerization of isoform 1 but prevents heterodimerization of isoform 1 and isoform 2. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0424941 – 243Missing in isoform 6. 1 PublicationAdd BLAST243
Alternative sequenceiVSP_0424951 – 159MRFRF…MHYSR → MIFNK in isoform 7. 1 Publication